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Neural systems underlying approach and avoidance in anxiety disorders
Open accessAbstract
Approach-avoidance conflict is an important psychological concept that has been used extensively to better understand cognition and emotion. This review focuses on neural systems involved in approach, avoidance, and conflict decision making, and how these systems overlap with implicated neural substrates of anxiety disorders. In particular, the role of amygdala, insula, ventral striatal, and prefrontal regions are discussed with respect to approach and avoidance behaviors. Three specific hypotheses underlying the dysfunction in anxiety disorders are proposed, including: (i) over-representation of avoidance valuation related to limbic overactivation; (ii) under- or over-representation of approach valuation related to attenuated or exaggerated striatal activation respectively; and (iii) insufficient integration and arbitration of approach and avoidance valuations related to attenuated orbitofrontal cortex activation. These dysfunctions can be examined experimentally using versions of existing decision-making paradigms, but may also require new translational and innovative approaches to probe approach-avoidance conflict and related neural systems in anxiety disorders.
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“The PFC likely regulates play in a multifactorial manner, contributing to expression of the behavior through its roles in suppressing aggression, monitoring approach/avoid conflict, and modulating the stress response via its projections to the MeA and other stress-modulatory nodes (Aupperle & Paulus, 2010; McEwen & Morrison, 2013; Takahashi et al., 2014).”
From Developmental origins of sex differences in the neural circuitry of play (2020) · cites this paper as Aupperle & Paulus, 2010
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“For example, anxiety disorders and mood disorders share hyperactive amygdala responses to negatively valenced stimuli [2,3]”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [2]
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Developmental origins of sex differences in the neural circuitry of play
VanRyzin, J. W., Marquardt, A. E., & McCarthy, M. M. (2020) · International Journal of Play · doi:10.1080/21594937.2020.1723370 · Cited by 34
“…behavior through its roles in suppressing aggression, monitoring approach/avoid conflict, and modulating the stress response via its projections to the MeA and other stress-modulatory nodes (Aupperle & Paulus, 2010; McEwen & Morrison, 2013; Takahashi, Nagayasu, Nishitani, Kaneko, & Koide, 2014).”
Oxytocin attenuates social and non-social avoidance: Re-thinking the social specificity of Oxytocin
Harari-Dahan, O., & Bernstein, A. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.04.005 · Cited by 34
“…research may be pursued among persons suffering from behavioral disorders mediated by approach-avoidance dysregulation broadly defined, such as anxiety-related disorders (e.g., Aupperle and Paulus, 2010); as opposed more socially-circumscribed mental disorders (e.g., Guastella et al., 2009).”
Hecht, E. E., Kukekova, A. V., Gutman, D. A., Acland, G. M., Preuss, T. M., & Trut, L. N. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.3114-20.2021 · Cited by 37
Bloem, B., Huda, R., Amemori, K., Abate, A., Krishna, G., Wilson, A. L., Carter, C. W., Sur, M., & Graybiel, A. M. (2022) · Nature Communications · doi:10.1038/s41467-022-28983-5 · Cited by 33
Relief learning is distinguished from safety learning by the requirement of the nucleus accumbens.
Mohammadi, M., Bergado-Acosta, J. R., & Fendt, M. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.06.053 · Cited by 35
Christian, C., & Levinson, C. A. (2022) · New Ideas in Psychology · doi:10.1016/j.newideapsych.2022.100964 · Cited by 33
Letkiewicz, A. M., Kottler, H. C., Shankman, S. A., & Cochran, A. L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105103 · Cited by 37
Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear
Kreuder, A., Scheele, D., Schultz, J., Hennig, J., Marsh, N., Dellert, T., Ettinger, U., Philipsen, A., Babasiz, M., Herscheid, A., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920147117 · Cited by 27
Unraveling the interplay between math anxiety and math achievement
Lau, N. T. T., Ansari, D., & Sokolowski, H. M. (2024) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2024.07.006 · Cited by 31
Mizumoto, T., Ikei, H., Hagiwara, K., Matsubara, T., Higuchi, F., Kobayashi, M., Yamashina, T., Sasaki, J., Yamada, N., Higuchi, N., et al. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.04.025 · Cited by 30
Blay, Y., Keshet, H., Friedman, L., & Gilboa‐Schechtman, E. (2020) · Personality and Individual Differences · doi:10.1016/j.paid.2020.110449 · Cited by 30
Frontostriatal Projections Regulate Innate Avoidance Behavior
Loewke, A. C., Minerva, A. R., Nelson, A., Kreitzer, A. C., & Gunaydin, L. A. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2581-20.2021 · Cited by 40
“, 2007), and several types of avoidance behavior (Green et al., 1967; Rothman and Glick, 1976; Aupperle and Martin, 2010; Aupperle et al., 2015; LeBlanc et al., 2018).”
Frederick, A. L., Saborido, T. P., & Stanwood, G. D. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00029 · Cited by 28
“…the neural circuits underlying these disorders are not completely understood, dysfunctions in the amygdala, hippocampus, basal ganglia, and prefrontal cortex are commonly implicated (Clark et al., 2009; Aupperle and Paulus, 2010; Clark and Beck, 2010; Harro et al., 2011; McEwen et al., 2012).”
Chrysikou, E. G., Gorey, C. M., & Aupperle, R. L. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw140 · Cited by 33
“…AAC decision-making may have important consequences for the conceptualization and treatment of anxiety disorders (Stein and Paulus, 2009; Aupperle and Paulus, 2010), which typically entail avoidance of short-term emotional discomfort, even at the cost of substantial long-term rewards…”
InfluentialDelta Opioid Receptors: Learning and Motivation
Pellissier, L. P., Pujol, C., Becker, J. A. J., & Merrer, J. L. (2016) · Handbook of experimental pharmacology · doi:10.1007/164_2016_89 · Cited by 30
“We propose that, in these animals, high levels of anxiety (avoidance) compete with high motivation for food (approach) to drive behavior(Aupperle and Paulus 2010; Montgomery 1955;Powell et al. 2004).”
Reilly, E. E., Whitton, A. E., Pizzagalli, D. A., Rutherford, A. V., Stein, M. B., Paulus, M. P., & Taylor, C. T. (2020) · Depression and Anxiety · doi:10.1002/da.23081 · Cited by 28
“Traditionally, anxiety disorders have been characterized by alterations in negative valence systems, with a relative neglect of the positive valence systems (Aupperle & Paulus, 2010; Insel et al., 2010).”
Ben‐Zion, Z., Shany, O., Admon, R., Keynan, J. N., Avisdris, N., Balter, S. R., Shalev, A. Y., Liberzon, I., & Hendler, T. (2021) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2021.09.001 · Cited by 28
Neural Correlates of Deficits in Humor Appreciation in Gelotophobics
Chan, Y. (2016) · Scientific Reports · doi:10.1038/srep34580 · Cited by 30
Aberg, K. C., Doell, K. C., & Schwartz, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0166675 · Cited by 28
Santiago, J., Akeman, E., Kirlić, N., Clausen, A. N., Cosgrove, K. T., McDermott, T. J., Mathis, B. K., Paulus, M. P., Craske, M. G., Abelson, J. L., et al. (2020) · Trials · doi:10.1186/s13063-019-3802-9 · Cited by 26
McDermott, T. J., Kirlić, N., Akeman, E., Touthang, J., Clausen, A. N., Kuplicki, R., & Aupperle, R. L. (2021) · Human Brain Mapping · doi:10.1002/hbm.25371 · Cited by 24
“Behavioral and neural responses during approach-avoidance conflict are important factors contributing to psychiatric disorders with pronounced affective disturbance (Aupperle & Paulus, 2010).”
Hillert, L., Jovanovic, H., Åhs, F., & Savic, I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054781 · Cited by 25
“The ACC is said to be primarily involved in signaling the presence of conflict, [12,13] and may, thus, very well show an enhanced activation when subjects with MCS condition were exposed to odors.”
Labrenz, F., Woud, M., Elsenbruch, S., & Icenhour, A. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.841734 · Cited by 22
“Psychosomatic disorders are characterized by approach-avoidance conflicts following a continuum between the subjectively perceived threat and associated costs (156).”
Butterfield, R. D., Siegle, G. J., Lee, K. H., Ladouceur, C. D., Forbes, E. E., Dahl, R. E., Ryan, N. D., Sheeber, L., & Silk, J. S. (2019) · Developmental Science · doi:10.1111/desc.12812 · Cited by 22
“Adolescent disengaged coping was opera‐ tionalized to include avoidance and distraction strategies because both of these strategies are known to contribute to the maintenance of anxiety (Aupperle & Paulus, 2010; Wright, Banerjee, Hoek, Rieffe, & Novin, 2010).”
Amemori, S., Graybiel, A. M., & Amemori, K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.649167 · Cited by 20
Impaired probabilistic reversal learning in anxiety: Evidence from behavioral and ERP findings
Xia, L., Xu, P., Yang, Z., Gu, R., & Zhang, D. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102751 · Cited by 18
“…these two regions have been considered to play important roles in the etiology of anxiety disorders (Grupe & Nitschke, 2013; Tovote et al., 2015) as well as in the relationship between anxiety and decision-making behavior (Amemori & Graybiel, 2012; Aupperle & Paulus, 2010; Krain et al., 2008).”
Association between reward-related functional connectivity and tri-level mood and anxiety symptoms
Anderson, Z. G., Damme, K. S. F., Carroll, A., Chat, I. K.-Y., Young, K. S., Craske, M. G., Bookheimer, S. Y., Zinbarg, R. E., & Nusslock, R. (2023) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103335 · Cited by 26
“Anxiety related findings are less consistent, but similar reductions in vS responses to rewarding stimuli have been noted (Auerbach et al., 2022; Robin and Martin, 2010).”
InfluentialGe, R., Zhang, S., & Zhao, H. P. (2022) · Information Technology and People · doi:10.1108/itp-12-2021-0927 · Cited by 22
Chowkase, A. A., Parra-Martínez, F. A., Ghahremani, M., Bernstein, Z. L., Finora, G., & Sternberg, R. J. (2024) · Frontiers in Psychology · doi:10.3389/fpsyg.2024.1376195 · Cited by 20
Neuroscientific Insights Into Management Development
McDonald, P., & Tang, Y. (2014) · Group & Organization Management · doi:10.1177/1059601114550712 · Cited by 20
Vignon, A., Dudon, G., Oliva, G., Thirard, S., Alenda, U. G., Brugoux, A., Cazevieille, C., Imbert, J., Bellières, C., Lehmann, S., et al. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.138640 · Cited by 22
Martínez-Rivera, F. J., Pérez-Torres, J., Velázquez-Díaz, C. D., Sanchez-Navarro, M. J., Huertas-Pérez, C. I., Diehl, M. M., Phillips, M. L., Haber, S. N., & Quirk, G. J. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.008 · Cited by 18
“…highlighted the role of the insular/orbital cortex in fi ne-tuning avoidance-based decisions in animals (12 – 16) and humans (including patients with OCD) (17 – 20), little is known about the in fl uence of the insular/ orbital cortex on prefrontal and limbic areas that modulate persistent avoidance.”
Smith, R. S., Lavalley, C. A., Taylor, S., Stewart, J. L., Khalsa, S. S., Berg, H. E., Ironside, M., Paulus, M. P., & Aupperle, R. L. (2023) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.220226 · Cited by 19
Konishi, J. S., Asami, T., Hayano, F., Yoshimi, A., Hayasaka, S., Fukushima, H., Whitford, T. J., Inoue, T., & Hirayasu, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092862 · Cited by 21
“Thus, the OFG integrates approach- and avoidance-valuations [22].”
Interrupting behaviour: Minimizing decision costs via temporal commitment and low-level interrupts
Lloyd, K., & Dayan, P. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005916 · Cited by 22
Rattel, J. A., Miedl, S. F., Liedlgruber, M., Blechert, J., Seidl, E., & Wilhelm, F. H. (2020) · Behaviour Research and Therapy · doi:10.1016/j.brat.2020.103761 · Cited by 18
Patt, V. M., Hunsberger, R., Jones, D. A., Keane, M. M., & Verfaellie, M. H. (2021) · PLoS ONE · doi:10.1371/journal.pone.0251480 · Cited by 19
Prepubertal gonadectomy reveals sex differences in approach-avoidance behavior in adult mice
Delevich, K. M., Hall, C. D., Boivin, J. R., Piekarski, D. J., Zhang, Y., & Wilbrecht, L. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104641 · Cited by 18
Bashford‐Largo, J., Aloi, J. M., Zhang, R., Bajaj, S., Carollo, E., Elowsky, J., Schwartz, A., Dobbertin, M. D., Blair, J., & Blair, K. S. (2021) · Depression and Anxiety · doi:10.1002/da.23150 · Cited by 18
“On the basis of suggestions that disrupted computations related to approach‐ avoidance decision‐making are implicated in the pathophysiology of GAD (Aupperle & Paulus, 2010), we hypothesized atypical recruitment of regions implicated in avoidance responses (e.g., dorsomedial frontal and anterior…”
InfluentialMcDermott, T. J., Berg, H. E., Touthang, J., Akeman, E., Cannon, M. J., Santiago, J., Cosgrove, K. T., Clausen, A. N., Kirlić, N., Smith, R. S., et al. (2022) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.220083 · Cited by 16
Metadata
- Authors
- Robin L., A., & Martin, P. P.
- Affiliations
- Department of Psychiatry, University of California, San Diego (UCSD), California, USA
- Psychiatry Service, Veterans Affairs San Diego Health Care System, San Diego, California, USA
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2010-12-31
- Volume
- 12
- Issue
- 4
- Pages
- 517-531
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC3181993
- OpenAlex
- W1574357942
- Cited by
- 227
- References
- 251
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 18 · 2023: 22 · 2022: 25 · 2021: 18 · 2020: 21 · 2019: 8 · 2018: 7 · 2017: 11 · 2016: 15 · 2015: 12 · 2014: 14 · 2013: 8 · 2012: 7
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- approach-avoidance conflict, anxiety disorders, decision-making, amygdala, insula, ventral striatum, orbitofrontal cortex
- MeSH terms
- Anxiety Disorders, Avoidance Learning, Brain, Decision Making, Emotions, Humans, Models, Biological, Social Behavior
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